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Neurotoxicity

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Description of key information

Oral (OECD 424), acute, rat: NOAEL (males/females) = 508 mg/kg bw 
Oral (OECD 424), subchronic, rat: NOAEL (males/females) = 592/748 mg/kg bw/day

Key value for chemical safety assessment

Effect on neurotoxicity: via oral route

Endpoint conclusion
Dose descriptor:
NOAEL
508 mg/kg bw/day

Additional information

The acute neurotoxicity study in rats was performed in accordance with OECD 424 (Gilmore, 2006). The test substance was administered by gavage to rats at analytical doses of 126, 508 and 2060 mg/kg for both sexes. The test substance was formulated in 0.5% methylcellulose / 0.4% Tween 80 in deionised water.

After treatment, no mortalities occurred. There was no evidence of neurotoxicity at any dose level and no compound-related gross or microscopic lesions at up to the highest dose tested were found. However, in high dose males and females (2060 mg/kg bw), urine staining was observed on day 0, but resolved the following day after treatment. Based on these finding, the NOAEL was 508 mg/kg bw.

 

In the subchronic neurotoxicity study conducted according to OECD 424, rats received the test substance dissolved in acteone in their diet over a period of 13 weeks (Gilmore and Hoss, 2006). The following doses were administered: 1000, 3000 and 9000 ppm of the test substance, corresponding to 65.2, 193, 592 mg/kg bw/day for males and 84.5, 251, 748 mg/kg bw/day for females.

There was no evidence of neurotoxicity or toxicity at any dose level and no compound-related gross or microscopic lesions at up to the highest dose level of 9000 ppm were found. For both sexes, there were no treatment-related effects on mortality, clinical observations, FOB, body weight and weight gain, food consumption, motor activity, ophthalmology or brain weight. Therefore, the NOAEL was determined to be 592 mg/kg bw/day for males and 748 mg/kg bw/day for females.

Justification for classification or non-classification

The available data on neurotoxicity of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.